Topping the gaps of the Allegheny, the area is one of only five major breaks in the Appalachians allowing east–west transportation corridors before the advent of 20th century technologies.

[a] Dutch traders and trappers friendly to the Susquehannock may have visited the region about 1620,[4] as the town sits atop a mountain pass through which the ancient Amerindian trails (later renamed the Kittanning Path) transited.

[7][8] By 1675, both the Susquehannocks and Erie tribes would both fall to rampant multiple-years of epidemic diseases, in combination with the vicious multi-decade internecine territorial bloodletting known as the Beaver Wars, which left the Alleghenies a remote hunting ground of the Five Nations of the Iroquois Confederation.

[10] By the late 1700s, the remnant Seneca and Cayuga that became known as the Ohio Iroquois or Mingo would have ranged the area, especially because they were known to make their towns along defensible hill tops and kept to the uplands.

By 1824, the visionary Main Line of Public Works legislation had been debated and signed and the construction of the Allegheny Portage Railroad soon began aiming to connect Pittsburgh and the Ohio Country to Philadelphia by canals.

Coal mining, the Pennsylvania Railroad yard in the town center and the production of coke were important industries.

The town still sports an important rail yard with a turning wye for helper engine turnaround and holds two rail tunnels leading east and downward from the yard trackage to the famous PRR Horseshoe Curve, whose upper approaches are within the town.

Gallitzin is located in eastern Cambria County at 40°28′55″N 78°33′8″W / 40.48194°N 78.55222°W / 40.48194; -78.55222 (40.481816, -78.552336),[13] along the eastern edge of the Allegheny Plateau, a highland area of hills and small streams formed differently from the Ridge-and-valley Appalachians to the east and south of the plateau's edge, the Allegheny Ridge in Pennsylvania.

Sitting astride the eastern Continental divide along the edge of the Allegheny Front escarpment, the immediate area is lower than other portions of the Appalachian Plateau, so contains several small streams and freshets forming the gaps of the Allegheny Escarpment to the east, where the ground falls away rapidly, forming steep terrain landforms.